Thrombin is perhaps the most potent agent to induce platelet secretion and aggregation. Because of its potency, this proteolytic role appears to be of extreme importance in forming platelet aggregates during hemostasis and thrombosis. The proposed research will establish the molecular mechanism of thrombin's interaction with the platelet which will provide a basis regulating the thrombin-platelet interaction. There are three immediate objectives to this proposal: 1. To identify the thrombin proteolytic receptor site on the platelet membrane surface. Recent studies from this laboratory have shown that one of the membrane glycoproteins (V) is hydrolyzed during thrombin-induced platelet stimulation. Experiments are described to a. test the hypothesis that glycoprotein V hydrolysis causes platelet stimulation and b. determine if any other platelet membrane proteins are hydrolyzed during this activation process. 2. To determine if thrombin binds to any other receptor on the membrane surface. It is proposed to use photoactive stable crosslinking reagents to covalently attach thrombin to its receptor site on the membrane. These reagents will be cleavable so that the receptor site can be identified. 3. To elucidate the membrane chemistry of thrombin activation. Methods are outlined for the isolation of the thrombin receptor and to determine how thrombin association with this receptor activates the platelets.